We have previously studied morphologic and physiologic alterations in the male reproductive tract after vasectomy in several species. In the proposed work we plan to determine whether vasectomy-induced changes are reversed by a subsequent vasovasostomy. The first aim of the proposed work is to determine the extent of alterations in the microscopic structure of the testis, the integrity of the blood-testis barrier and structure and physiology of the epididymis and vas deferens in vasectomized animals and in animals subjected to vasectomy followed later by vasovasostomy. The second aim is to determine the extent to which the loss of fertility after vasectomy can be restored by vasovasostomy, and to relate the fertility status of individuals to the persistence or reversal of anatomic and physiologic changes in the reproductive tract. The third aim is to determine whether increases in serum antisperm antibodies generated after vasectomy are affected by vasovasostomy and whether restoration of fertility is correlated with a decline in antibody levels. The study will be carried out in the Lewis rat because these animals rapidly acquire testicular lesions and serum antisperm antibodies after vasectomy. Our studies combine morphological, physiological and immunological approaches. Young adult male rats will be subjected to bilateral extrascrotal vasectomy. Three months later a microsurgical vasovasostomy will be performed. Animals will be maintained for 1 or 4 months after vasovasostomy. One group of controls will receive sham operations, while a second group of controls will receive a vasectomy but no vasovasostomy. Methods include micropuncture light and electron microscopy, and measurement of intraluminal hydrostatic pressure. The blood-testis barrier will be studied by lanthanum tracer experiments, freeze-fracture, and transepithelial transport of 3H-inulin. Patency of the anastomosis after vasovasostomy will be investigated by microscopy and by measuring its resistance to fluid flow. Immunologic studies will employ three tests for serum antisperm antibodies: sperm agglutination, immunofluorescence, and a solid phase immunofiltration microtiter assay.